SIMULTANEOUS MONITORING OF THE SEIZURE-RELATED CHANGES IN EXTRACELLULAR GLUTAMATE AND GAMMA-AMINOBUTYRIC-ACID CONCENTRATION IN BILATERAL HIPPOCAMPI FOLLOWING DEVELOPMENT OF AMYGDALOID KINDLING

We simultaneously monitored the seizure-related changes in extracellul ar hippocampal glutamate (Glu) and gamma-aminobutyric acid (GABA) conc entration in brain dialysates in order to clarify the role of Glu and GABA in the development of kindling. Brain dialysates were collected e very 5 min from 10 min prior to 80 min after stimulus in the three dev eloping conditions consisting of pre-kindling state, stage 3 (C-3), an d five consecutive stage 5 (5C-5) following kindling in the same rat. Extracellular Glu level increased rapidly, lasting for only 5 min aft er stimulus. The post-stimulus ratio of Glu increase in partially kind led rats (C-3) was 2.5-3.5 times of the baseline, and in fully kindled rats it was about 5 times of the baseline. Extracellular GABA concent ration enhanced gradually, reaching a plateau level at 15-20 min and l asting for several hours after stimulus at each stage. The enhancement of GABA level was about 1.5 times of the baseline in partially kindle d stage, and was about 2.5 times of the baseline in fully kindled stag e. There was no significant difference between the two hemispheres wit h respect to either the time-course or the magnitude of Glu and GABA i ncrease respectively. These data show that progressive, transient and stimulus-induced enhancement of extracellular Glu levels combined with long-lasting elevation of extracellular GABA levels in the bilateral ventral hippocampi results in imbalance between the excitatory and inh ibitory neuronal systems, causing excessive propagation of seizure act ivity, culminating in the secondary generalized seizure of amygdaloid kindling.